Background: Investigating factors contributing to chemistry achievement is important since it enables us to make more concrete instructional decisions related to improving students' chemistry achievement. Purpose: This study aimed to investigate how students' perceptions of learning environment, self-efficacy and gender are related to chemistry achievement. Sample: Three hundred fifty six high school students with the age range of 14 and 19 from three different schools in the same district were the participants. Design and methods: A structural equation model was designed and tested. Constructivist learning environment survey, self-efficacy scale were the instruments of the study. Information about students' gender and their chemistry grades belonging to the previous semester were also collected. Results: The model testing showed that chemistry self-efficacy beliefs, students' perceptions of constructivist learning environment (through chemistry-self efficacy) and gender were significantly related to chemistry achievement. Moreover, the findings showed that students' chemistry self-efficacy beliefs mediated the relation of students' learning environment perceptions to their chemistry achievement. Conclusions: The present study has some educational implications for teachers, teacher educators and curriculum developers. First of all, self-efficacy was found to have an effect on students' achievement. Therefore, teachers should consider students' self-efficacy beliefs and devise their instruction accordingly. Another implication of this study is the necessity of considering gender differences in designing teachers' instruction.