Objective: Primary objective of this study was to evaluate anti-inflammatory effect of caffeine in complete Freund's adjuvant model of rheumatoid arthritis. Secondary objective was to compare the topical anti-inflammatory action with systemic action of caffeine and to minimize many psychotropic effect of caffeine in normal individual or arthritic patient due to systemic administration and more emphasis on topical use of caffeine as an anti-inflammatory (TNF-α blockers).Methods: Arthritis was induced by a single sub-plantar injection (0.1 ml) of CFA into the left hind paw. Rats were treated with dexamethasone (0.05 mg/kg, p. o.), caffeine (20 and 50 mg/kg, p. o.) and caffeine gel (3% and 7% topical) from day 0 to day 12. Efficacy was evaluated by change in paw volume, serum C-reactive protein (CRP), estimation of serum rheumatoid factor (RF), arthritis index, and body weight and by histopathology of synovial joint. Results: CFA showed significantly (p < 0.001) higher paw volume, CRP, RF and arthritic index as compared to caffeine 20 mg/kg, caffeine 50 mg/kg, caffeine gel 3% and caffeine gel 7% treated animals. It was observed that topical caffeine gel (3% and 7%) suppressed paw volume, CRP, RF and arthritic index in a more statistically significant manner compared to oral caffeine solutions (20 mg/kg and 50 mg/kg).Conclusion: Topical caffeine gel (3% and7%) shows more significant anti-inflammatory effect as compared to oral caffeine solution (20 mg/kg and 50 mg/kg). Â
