Background:  The development of nanotechnology has been a boon to mankind as its significance paved the way for several applications in therapeutics. This study was to evaluate the anti-arthritic capability of nano Selenium-lovastatin mixture (Lov-Se) against inflammatory cascade in arthritic irradiated rats. Materials and Methods: Animal model of Arthritis was organized by subcutaneous injection of Complete Freund’s adjuvant; CFA. Rats were exposed to γ-radiation (2Gy every 3 days up to total dose of 8 Gy). Lov-Se (1ml ≈ 20 mg kg⁻¹ day⁻¹Lov and 0.1 mg kg⁻¹ day⁻¹Se) was administrated by daily oral injection. The antioxidant parameters (heart glutathione peroxides; GSH-Px, catalase; CAT, superoxide dismutase; SOD, xanthine dehydrogenase; XDH, reduced glutathione; GSH and blood selenium; Se), oxidant markers (heart Xanthine oxidase; XO, Nitric oxide; NO, protein carbonyls and thiobarbituric acid reactive substances; TBARS) and the inflammatory molecules (serum tumor necrosis factor-alpha TNF-α, C-reactive protein; CRP and rheumatoid factor; RF) were determined. Results: The arthritic and arthritic irradiated rats were displayed augment oxidative stress, inflammatory cascade and impaired antioxidant status compared to control. Conclusion: The data revealed that Lov-Se administration ameliorate oxidative, antioxidants parameters as well as inflammatory factors. The prolonged administration of Lov-Se mixture in appropriate concentration could exert a considerable systemic anti-inflammatory action through adjustment of red-ox tone and the integration of XDH/XO ratio.