The aim of this research was to examine the effect of students’ critical thinking skills using a guided inquiry model with macromedia flash and direct instruction in chemistry learning. The researchers used a quasi-experiment, with post-test only control group design. This research was conducted at SMAN 3 Kota Ternate. The research subjects were 50 experimental group students and 46 control group students. The data were collected through critical thinking test with seven description questions to see the student’s critical thinking skills that have been implemented. Then, the data were analyzed using ANOVA test statistics. The results of media validation were categorized into good and feasible, obtained from the validation test by media experts and material experts. The analysis of critical thinking skills test revealed that there is an increase in students’ critical thinking skills using a guided inquiry model with macromedia flash.