Abstract: Background: The side effects of anti-inflammatory agents considered as a major problem during their clinical use; therefore, development of newer and more effective and safe anti-inflammatory drugs is necessary. The present study was designed to evaluate the dose-response relationship of the anti-inflammatory activity of pentoxifylline in experimental animal models of chronic inflammation. Methods: Seventy two rats were allocated into nine groups, each containing 8 rats, for the study of the anti-inflammatory activity of pentoxifylline in experimental animal model of formalin-induced chronic inflammation; another 16 rats were used, and allocated into two groups, for the study of the anti-inflammatory activity of pentoxifylline (4.0 mg kg-1) when used in combination with dexamethasone or methotrexate. Fifty four rats were allocated into nine groups, each containing 6 rats, for the study of the anti-inflammatory activity of pentoxifylline in experimental animal model of cotton-pellet induced granuloma; another 12 rats were used and allocated into two groups, for the study of the anti-inflammatory activity of pentoxifylline (4.0 mg kg-1) when used in combination with dexamethasone or methotrexate. Results: Pentoxifylline significantly suppress inflammation in experimental animal models of formalin-induced chronic inflammation and cotton-pellet induced granuloma. Pentoxifylline (4.0 mg kg-1) in combination with dexamethasone significantly suppress inflammation in rat model of formalin-induced chronic inflammation and cotton pellet-induced granuloma which is significantly higher than all of the effects produced by other approaches of treatments. Conclusion: Pentoxifylline, in a dose dependent pattern, attenuates formaldehyde-induced chronic inflammation and cotton-pellet induced granuloma in rats and potentiates the anti-inflammatory activity of dexamethasone and methotrexate.