The third generation cephalosporin with a broad spectrum bactericidal activityof cefiximetrihydratein transdermal matrix patches were prepared by Solvent casting method using cross linkedpolymers with Chitosan and Sodium alginate with or without permeation enhancer and the patches wereevaluated and found to be having good physicochemical properties. The cumulative percentage of drugpermeation without and with permeation enhancer after 24 h through rat skin was found to be (FS-1 to FS-4) 49.40% to 50.84% and (FPE-1 to FPE-4) 75.48 % to 88.38 %. The kinetic profile show that thedrug release followed zero-order kinetics and well fits with Higuchi‟s model and followed by non-fickiandiffusion mechanism of drug release. The drug permeation rate (flux) 28.7315mcg/hr/sq.cm and enhancement ratio (1.6465) was found to bemaximum in the formulation FPE-2. Further, selected for in-vivo study of FPE-2 formulation and compared withoral suspension by using the rats, the results shows after 24 h 82.91% and 28.04%. The invitro-invivo correlation of FPE-2 was found to be 0.969, which indicates that not super-imposableand linear.