The objective of the research work to design, optimize, evaluate oral control release mucoadhesive microspheres of Tenofovir disoproxil fumarate. To design & formulate mucoadhesive microsohere of Tenofovir disoproxil fumarate by ionic gelation technique using few selected mucoadhesive polymer like sodium alginate, carbapol, chitosan & release retardant polymer for extended release like cmc and HPMC. Tenofovir prepared by using ionc gelation technique by using different ratios of polymer. One is cross linking polymer (Sodium alginate) and other is mucoadhesive polymers (HPMC, CMC, Carbapol). The microspheres were evaluated by different evaluation parameters like- drug entrapment efficiency, swelling index, micromeritics property, in vitro wash off test, in vitro drug release study and stability study. Drug content and entrapment efficiency of different formulation was found to be in the range of 82 to 95%. Swelling index of microspheres prepared as per experimental design were found to be satisfactory. In vitro wash off test showed that prepared microsphere exhibit for mucoadhesive properties. It was found that formulation with drug polymer ratio 1:2 released maximum amount of drug at 12hours. But the other formulation release the drug before 12 hours. Show that in comparison to all the 9 formulations F7 showing controlled release action.