The purpose of the study was to investigate the effectiveness of case-based learning instruction over traditionally designed chemistry instruction on eleventh grade students' epistemological beliefs and their attitudes toward chemistry as a school subject. The subjects of this study consisted of 63 eleventh grade students from two intact classes of an urban high school instructed with same teacher. Each teaching method was randomly assigned to one class. The experimental group received case-based learning and the control group received traditional instruction. At the experimental group, life cases were presented with small group format; at the control group, lecturing and discussion was carried out. The results showed that there was a significant difference between the experimental and control group with respect to their epistemological beliefs and attitudes toward chemistry as a school subject in favor of case-based learning method group. Thus, case base learning is helpful for development of students' epistemological beliefs and attitudes toward chemistry.