The main purpose of this study was to investigate the effectiveness of 5E instructional model of constructivist approach on grade seven students’ conceptual understanding of muscular and skeletal system concepts at Ewket Fana primary school. Quasi-experimental research design was employed. Out of four grade seven sections, two sections (N=122) were selected randomly and assigned as experimental (N=61) and control (N=61) groups. The students in the experimental group were instructed with the 5E instructional model of constructivist approach, and students in the control group were instructed with traditional teaching instruction for three weeks. Muscular and skeletal system concepts test, classroom observation and informal classroom assessment were used as data collection instruments. Pretest and posttest were analyzed quantitatively (descriptive statistics and t-tests) while classroom observation and informal classroom assessment were analyzed qualitatively. The pretest results indicated that there was no significant mean difference between experimental and control group students at P>0.05. The posttest comparison of students’ in the experimental group exhibited significant changes in conceptual understanding of the concepts compared to control group students at P<0.05. Similarly, the post informal classroom assessment comparison of students’ in experimental group showed a higher explaining and reasoning ability of the concepts compared to the control group. From the results, it is possible to conclude that the 5E instructional model of constructivist approach was more effective than the traditional teaching instructional in students’ conceptual understanding. Based on the finding the researcher suggested that curriculum developers should incorporate constructivist strategy of 5E learning cycle model into the biology curriculum as an instructional model for teaching biology.