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Background: Calophyllum (Clusiaceae) plants have been used as traditional medicine for rheumatism, vein problems, hemorrhoids, and gastric ulcers. The traditional uses of this genus prompted us to investigate six Malaysian Calophyllum species which are Calophyllum inophyllum, Calophyllum soulattri, Calophyllum lowii, Calophyllum teysmannii, Calophyllum benjaminum and Calophyllum javanicum for their anti-inflammatory properties. Materials and Methods: The stem bark of six plants was extracted with n-hexane (Hex), ethyl acetate (EA), and methanol (MeOH). The activities of the extracts were evaluated by determining the inhibition of nitric oxide (NO) production by lipopolysaccharide-induced RAW 264.7 cells, as well as protein denaturation. Results and Discussion: The C. lowii extracts showed the most significant activities against NO production with IC50values of <40 μg/mL. For the protein denaturation test, C. teysmannii extracts showed the strongest effect with IC50values of <100 μg/mL. The results indicated that C. lowii and C. teysmannii are effective in both assays. Besides, the Hex extracts of these Calophyllum plants possess stronger activities than the EA and MeOH extracts. The anti-inflammatory properties are contributed by the secondary metabolites present in the crude extracts, specifically flavonoid, triterpenes, and xanthones. Conclusion: These results confirm the potential of Calophyllum plants to serve as lead agents in preventing inflammation. Abbreviations used: NO: Nitric oxide; spp.: Species; Hex: Hexane; EA: Ethyl acetate; MeOH: Methanol. [ABSTRACT FROM AUTHOR]