Background: Diabetic nephropathy (DN), is the major health problem and various mechanism involved in the DN pathogenesis, abnormalities in the renal nitric oxide and inflammation has attracted a lot of attention. Various researches suggest that the micro-inflammation generated during the DN and the anti-inflammatory drug play a momentous role. The researcher targeted the NF-Kb mechanism for the treatment of DN. In the present study, we try to explore the molecular mechanism of Solid lipid nanoparticles (SLN) of qurectin in experimental induced DN in Streptozotocin (STZ) treated rats. Material & method: For SLN preparation, double emulsion displacement method was used. STZ (55 mg/kg) was used for the induction of DM and rats were divided into different group and received the treatment of QE and QE-SLN for 4 weeks. The body weight, plasma insulin, biochemical, antioxidant parameters were estimated, respectively. Pro-inflammatory cytokines viz., TNF- α, IL-1β and IL-6 inflammatory mediator nuclear transcription factor-kappa B (Nf-kB) and PGE2 were scrutinized, respectively. NF-κB, IL-6 and TNF-α expression of renal were also estimated, respectively. The renal tissue was further used for the histopathological observation. Result & discussion: QE-SLNs were evaluated for potential entrapment, particle size, drug release stability and gastric stability. QE-SLNs treatment demonstrated the down-regulation of blood glucose level and up-regulation of plasma insulin (25%), body weight (20%). Additionally, QE-SLNs treatment modulated the biochemical and antioxidant parameters. QE-SLNs treatment exhibited decreased level of IL-1β (32%), TNF-α (41%), IL-6 (29%), PGE2 (34%) and Nf-kB (42%). Moreover, QE-SLNs showed the alteration in the expression of TNF-α and Nf-kB. Histopathology suggests the less necrosis, infiltrated blood vessels and less swelling in vessels. Conclusion: We can conclude that QE-SLNs nano-formulation can prevent the Diabetic nephropathy via alteration of Nf-kB pathway.