A set of twenty-six compounds 2-Aryl pyridine derivatives with antirheumatoid activity was subjected to the two dimensional quantitative structure activity relationships studies using V life molecular drug design suit. Drug Designing module describe with various combinations of molecular connectivity indices, electro topological indices, alignment independent descriptors and other 2D descriptors. 2-Aryl pyridine taken as the lead molecule and QSAR model developed using multiple regression approach. For each set of descriptors, the best multi-linear QSAR equations were obtained by the stepwise variable selection method using leave-one-out crossvalidation as selection criterion. Logarithmic inverse value of IC50 was taken as dependent variable and parameters slogP and T_C_O_2, T_T_N_1, T_N_Cl_4, T_N_F_6 topological parameter was taken as independent variable. The best QSAR model (r2 = 0.8850, F = 23.08, r2 se = 0.14, q2 se = 0.222, Pred_r2 = 0.2307, pred_r2se = 0.3226) has acceptable statistical quality and predictive potential as indicated by the value of cross validated squared correlation coefficient (q2 = 0.75. Thus this validated model brings important structural insight to aid the design of novel anti- rheumatoid activity.