The Present study was undertaken with an aim to formulate and evaluate gel formulation of Diclofenac diethylamine using different polymers with the addition of penetration enhancers. Preformulation study was carried out initially and results directed for the further course of formulation based on the Preformulation studies different batches with polymer addition were prepared using selected excipients. Permeation enhancement of Diclofenac diethylamine was done by addition of DMSO and ethanol.The Diclofenac diethylamine gel formulation was optimized on the basis of different physical parameters and mainly with the comparison of formulations on the basis of in vitro diffusion study, permeability parameters and anti-inflammatory activity. The optimized gel formulation F14 was transparent, while marketed was creamy white in nature. Formulation F14 was the optimized formulation among all formulations.