To study the effects of teaching self regulation strategies and strengthening the self-efficacy on the students' academic performance, a sample of 280 high school freshmen (141 girls, 139 boys) were selected in two high schools in Shiraz, and then divided into four groups (control, direct instruction, cooperative, and independent study) in each school. The treatment consisted of a two-month self-regulation and self-efficacy course conducted in different ways. All groups completed the MSLQ (Motivational Regulation Strategies Questionnaire), The SEBQ (Self-efficacy in Biology Questionnaire), and the BAT (Biology Achievement Test) both before and after the treatment.ANCOVA results showed that the independent study group had the best grades in self-regulation and self-efficacy, while, as expected; the control group had the worst. There was no significant difference between the treatment level of 'direct instruction' and the control level. As for the academic performance in biology course, the independent study group was significantly higher than the three other groups that exhibited no significant difference among themselves. The results are discussed with respect to their implications for self-regulation and self-efficacy theories, future research, and educational systems.