This research paper describes the objective of the present study to formulate ophthalmic mucoadhesive in situ gelling system of Dorzolamide Hydrochloride using two different polymers namely Poly Acrylic Acid and Xanthan Gum, individually and in combinations. Cellulose (HPMC) was used as viscosity enhancing agent. The developed formulations were subjected to several evaluation parameters including physico-chemical properties, compatibility, in-vitro drug release, microbiological, ex-vivo and stability testing and compared with marketed formulation wherever possible. All formulations were found to be milky with pH between 6.0 to 6.5 for sols and nearly neutral for gels. All formulations showed instantaneous gelling with translucent gel matrix which retained its integrity for extended period of time. The viscosity of best formulation (F4) was found to be 20 cps. The drug was compatible with both the polymers and the viscoliser in both solid as well as liquid states. Invitro drug release studies showed that all the formulations released drug over a period of 12 hours with formulation F4 (0.2% w/v Xanthan Gum) showing the highest drug release of 90.84% of Dorzolamide Hydrochloride. All the formulations showed zero order drug release with the release mechanism being diffusion along with erosion of gel matrix for all formulations. Further the drug release from all the formulation was observed to be nonfickian. The best batch showed ex-vivo drug release through goat’s cornea for 9 hours with the release kinetics being similar to those seen with in-vitro drug release. All the formulations were found to be sterile.