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As a basic science discipline of the Pharmacy curriculum, Physiology could be used as a starting point with respect to incorporating clinical relevance as well as developing problem-solving skills of the pharmacy student. PBL methodology makes students more creative and constructive and helps them to develop knowledges, skills, behaviours, and attitudes that prepare them in their professional life to be good practicing pharmacists. Our current practical Physiology program provides students with the opportunity to gain a first-hand laboratory experience of the structure, function, and development of the digestive system. By using of both the simulation PhysioEX 9.0 software as a virtual laboratory and the histological analysis of the digestive structures, students learn to integrate human anatomy and physiology. In this study, a mixed-methods approach was adopted including PBL as a planning practical course strategy. We compared the degree of satisfaction and academic achievement of students from second-year pharmacy students enrolled in the practical physiology course, one group including problem-based learning (PBL) and another one without PBL (Non-PBL) method. Students performed the tasks in small groups of 3-4 students. All of them used the simulation virtual laboratory where they evaluated the activity and function of the digestive enzymes and also carried out the histological study of the different areas of the digestive system. For the PBL group, two case problems were designed and delivered in the Virtual Campus with enough time for its completion by self-learning using students own bibliography. During the practical session, the students with PBL clarified case-problem terms with a brainstorm about the possible explanations, identified learning solutions and questions and the subsequent discussion to integrate the individual results from their self-study with those found from simulation and histological analysis. The non-PBL students were enrolled in the traditional class conducted by lectures. Student feedback was received based on a questionnaire in the five-point Likert scale format. The satisfaction questionnaire evaluated and compared the opinions of the students in twenty fields of learning and the interaction between the applied learning methods. The feedback revealed a majority agreement that PBL helped students create interest, better understanding and promotes critical thinking. Cronbach's alpha reliability coefficient were 0.825 (PBL) and 0.929 (not PBL), respectively. The results of our study clearly showed that PBL condition had significantly higher mean scores. In addition, to evaluate whether the mixed PBL method helped to solve the posed clinical case-problems, Pre and Post-test score statistical analysis was performed. A substantial improvement in post-test results clearly revealed PBL's acceptance. Students learned to correlate relevant enzymatic mechanisms, histological, and clinical features with the clinical signs and symptoms, to learn the digestive physiology. PBL integrated with conventional learning methods would be more effective at helping student to learn and to have an integrating vision of the functioning of the physiological systems which can be applied in the professional context as future pharmacist.