Abstract: Background and Objective: Methylprednisolone (MP) inhibits secondary inflammations associated with spinal cord injury (SCI), however, its effectiveness is required to be improved because it shows higher protein binding if administered orally or intravenously. Therefore, this study aimed to develop solid lipid nanoparticles (MSLN) based semisolid hydrogel of MP to ensure maximum drug availability at the spinal cord injury site following local administration. Methodology: The MSLNs were prepared by pre-emulsification ultrasonic probe sonication method. The MSLN was characterized on the basis of entrapment efficiency, particle size, surface charge, polydispersity index and morphological characteristics. Further, Carbopol 940 gel of MSLN (MSLNG) was by pH sensitive gelling. The MSLNG was evaluated for in vitro release, in vitro cytotoxicity and in vivo potential against post SCI like conditions. Results: Shape of MSLN was spherical and surface was smooth. Droplets of size, zeta potential and polydispersity index were 76.7±7.8 nm, -26.7 mV and 0.231, respectively. Its entrapment efficiency was observed to be 48.9%. Viscosity and pH of the gel were 88205±47.72 cP and 4.68, respectively. The MSLN retained cells were more viable as compared with drug solution at the same dose. Release of the drug from MSLNG was observed to be controlled as compared to gel of drug solution (MPG). The MSLNG and MPG were able to reduce the level of cytokines such as Il-1β and TNF-α but only MSLNG showed significant change in the level of cytokines. Based on behavioral data assessment and histopathological investigations, MP delivery through MSLNG was found to be more effective in treating post SCI conditions when compared with MPG. Higher efficacy in the case of MSLNG could be due to the controlled release of MP at local site. Conclusion: Lipid based hydrogel of MSLNG was developed successfully which might offer safe and effective mean for the treatment of post SCI like conditions.