Thiocolchicoside has a selective affinity for g-amino-butyric acid (GABA) receptors and acts on themuscular contracture by activating the GABA-nergicinhibitory pathways thereby acting as a potent muscle relaxant Thiocolchicoside (Muscoril, Myoril, Neoflax) is a muscle relaxant with anti-inflammatory and analgesic effects. It is used for the treatment of orthopedic, traumatic and rheumatologic disorders.This drug can not be absorbed oraly owing to its very less permeation through GI epithelia. The physico chemical properties of thiocolchicoside are not favorable for its permeation across the skin. Thiocolchicoside has a relatively high molecular weight (563), relatively high water solubility (16.1mg/ml) and low octanol/water partition coefficient (log P=-0.34). The present study attempts to increase the intestinal permeability of BCS class III drug Thiocolchicoside by using certain intestinal absorption enhancers. To enhance the permeation, intestinal permeation enhancers were used in various molar ratios with the drug. The liphophilicity of Thiocolchicoside was determined by means of the n-octanol/water syatem to check the effect of absorption enhancers. The changes in partition coefficient by the octanol/water system were confirmed using an invitro transport model with the excised animal tissue membrane. The Data Expert software is applied for the 32 factorial designand the ANOVA study of the linear regression model, response surface plot as well as contour plot confirms the predicted batch with the desirability of 0.982.Result of R2 and T-test confirmed that predicted and observed responses showed no significant difference. The result indicated that there is significant improvement in the permeability of the drug and the extent of enhancement was highly dependent on the type of absorption enhancers used. Thus the study indicated that Thiocolchicoside could be successfully delivered orally when formulated with permeation enhancers.