The overexpression of cyclooxygenase-2 (COX-2) enzyme has been strongly contributed to tumorigenesis. The efficacy of celecoxib as a selective COX-2 inhibitor has been shown in many studies, but the underlying mechanism as a chemopreventative agent has not yet been well known. For better understanding the chemopreventative molecular mechanisms, we used a comparative proteomics analysis of lipopolysaccharide (LPS) treated and untreated J774.A1 macrophage-like cell lines before and after treatment with celecoxib. Our findings define the contribution of several interesting proteins, including ferritin heavy chain, glyoxalase-1, cofilin, vimentin, and galectin-1, which could extend our understanding of the chemopreventative effects of celecoxib and provide new valuable tools for further anticancer research.