The aim of the study is to explore the effect of quercetin-loaded solid lipid nanoparticles on trauma therapy and scar inhibition and its related mechanism. Brain external skin of SD rats was removed. Masson staining, Sirius Red staining and scanning electron microscopy was used for the evaluation of the effect of quercetin solid lipid nanoparticle on traumatic repair and scar inhibition. The astrocyte migration model was used to investigate the effect of quercetin. Western blotting was applied to determine the expression of TGF-β1, TGF-βRI, TGF-βRII, Smad2, Smad3, Smad4 and Smad7 in traumatic skin and astrocytes. The repair rate of traumatic skin in groups QL and QS was significantly higher than that in groups C and CS (P<0.05) after 7 days, 14 days and 21 days of administration. Quercetin solid lipid nanoparticles significantly inhibited the proliferation and migration of astrocytes (P<0.05). Compared with C group, the relative expression of TGF-β1, TGF-βRI, TGF-βRII, Smad2, Smad3, Smad4 and Smad7 did not significantly in astrocytes and skin tissue of CS (P>0.05). Compared with groups C and CS, the relative expression of TGF-β1, TGF-βRI, TGF-βRII, Smad2, Smad3 and Smad4 in astrocytes and skin tissue of QL and QS were significantly decreased and the relative expression of Smad7 was significantly increased (P<0.05). Quercetin solid lipid nanoparticles can inhibit the activation of TGF-β/Smad pathway, accelerating the wound repair and inhibiting the formation of scar.