Process Oriented Guided Inquiry Learning (POGILs) as a collaborative inquiry method has been widely used in teaching chemistry to high school and college students. This paper presents the impact of POGIL on 65 middle school students’ understanding about nature of matter. It is a quasi-experimental non-equivalent control group design study in which a control group taught by whole class instruction was compared to the experimental group which was taught by POGIL in the context of the ‘‘Particulate Nature of Matter (PNM) Unit’’ including PNM, physical and chemical change and density topics. A Nature of Matter Achievement Test was administered as both pre- and post-test. It was found that a POGIL method improved students’ achievement more than teacher-centered whole-class instruction. This study provides evidence supporting the fact that POGIL is an effective pedagogy to teach nature of matter to middle school students.