Objective: To analyze the effects of the topical gel that consists of quercetin nanoparticles on the mono iodoacetate-induced osteoarthritis. Methods: Injection of lecithin-quercetin into chitosan-tocopheryl polyethylene glycol succinate (TPGS) was used to prepared quercetin nanoparticle. Evaluation parameter for the quercetin nanoparticle including polydispersity index, zeta potential, particle size using particle size analyzer and morphology were executed using a transmission electron microscope. The evaluation of quercetin nanoparticle gel includes organoleptic and also a homogeneity of quercetin nanoparticle gel includes pH and viscosity. Quercetin nanoparticle gel was given for osteoarthritis (OA) animal model. The amount dosage of quercetin nanoparticle used in this study was 0.84, 1.68, and 3.37 mg/g gel. Measurement of the edema volume was conducted on day 7, 14, 21, 28, 35, 42, 49, 56, 63, and 70. Results: The quercetin nanoparticle gel dosage 1, 2, and 3 could reduce inflammation on two osteoarthritis animal models. On DMM group, 14 d after the treatment, there were significant differences between negative group and dosage 3 (P=0.028) and A. conyzoides extract gel (P=0.015). It has shown that injection of mono iodoacetate intraarticularly significantly increased the volume of edema in all groups that had been given by mono iodoacetate on day 7 to day 28. On the 42 d after administration of quercetin nanoparticle gel, there were significant differences between the normal and dosage 3 group (P= 0.000). Conclusion: Quercetin nanoparticle gel could reduce inflammation and prevent cartilago damage on histological evaluation.