The aim of this study was to assess mechanism of miR-155 carried with nanoparticles and Dexmedetomidine in regulating oxidative stress and inflammation in rats with gonitis. Model of rats with gonitis was established and rats were treated by miR-155 nanoparticles and Dexmedetomidine (Dex) or combined method. The rat weight growth rate (WGR), toe swelling, and arthritis index were then analyzed. Proliferative and apoptotic conditions were detected, while expression levels of IL-18 and IL-1β were detected with enzymelinked immunosorbent assay (ELISA) method. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were analyzed, and expression level of NF-κB was detected with Western Blot assay. The rats with WGR in the treated sets were improved, while toe swelling and arthritis index were reduced. Moreover, proliferation was restrained and apoptosis was prompted. The MDA content was reduced while SOD activity was increased, and expression levels of IL-18, IL-1β, and NF-κB were reduced. The action in the combined set was more notable, while the NF-κB signal pathway and secretion of inflammatory factors were restrained by the miR-155 nanoparticles and Dex. Finally, the oxidative stress was improved, while inflammation was restrained, and symptom of gonitis were improved.