This study explores a topical hydrogel incorporating mesoporous silica nanoparticles (MSNs) loaded with etodolac (ETD) for inflammation treatment. MSNs were synthesized via the sol-gel method and loaded with ETD using adsorption. The ETD-MSNs were formulated into a gel using Carbopol® Ultrez. Characterization confirmed an average size of 254.9 nm, a zeta potential of -38mV, and high porosity. The encapsulation and loading efficiencies were 23.92 % and 28.12 %, respectively. In vitro drug release showed 93.60±1.31 % cumulative release at 8 h. In vivo studies in a Complete Freund’s Adjuvant (CFA) induced arthritic rat model demonstrated significant reduction in inflammation, articular damage and pannus formation. The gel outperformed marketed Proxym® gel in reducing paw edema. Stability studies confirmed no significant changes over 3 months. These findings highlight the potential of ETD-MSN hydrogel as an effective anti-inflammatory treatment with sustained drug release and enhanced therapeutic efficacy.