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The objective of the present study was to evaluate the effect of Berberis aristata(BA) against oxazolone induced contact dermatitis in Balb/c mice and molecular docking with TLR-1 and TLR-2. Dermatitis was induced in Balb/c mice by sensitizing with topical application of 100 μl oxazolone (2%) and the effect of BA was screened in two doses (200 mg/kg and 400 mg/kg P.O.). The effect was evaluated by the change in ear thickness, anti-inflammatory cytokine (TNF-α, IL-6, and IL-1β) and oxidative stress on the sixth day in ear tissue homogenate. The ear skin of all group mice was subjected to histological analysis. This work was further evidenced by the docking of berberine with crystal structure of TLR1-TLR2 heterodimer caused by using the binding of tri-acylated lipopeptide (PDB ID: 2Z7X). In this study, we found that a significant reduction in ear thickness was found in BA (200 mg/kg and 400 mg/kg) as compared to 100 μl oxazolone(2%) treated mice. The reduction level of GSH and SOD found in 100 μl oxazolone (2%) sensitized mice. BA (200 mg/kg and 400 mg/kg) treated animals showed an increase in GSH and SOD levels. A significant reduction in inflammatory cytokines was observed in BA treated mice and indicates anti-inflammatory activity against oxazolone. Histopathological analysis showed minimal infiltration of lymphocytes and moderate harm to skin cells and layer in BA treated mice. Docking studies revealed promising binding interaction of berberine withTLR1-TLR2 heterodimer which can attribute to its anti dermatic effect. This present research shows that BA has a dose-dependent effect in contact dermatitis attenuated by oxazolone.