The protozoan parasite Toxoplasma gondii (Tg) is a ubiquitous organism capable of infecting a wide range of vertebrate hosts including man. Toxoplasmosis is the disease caused by Tg. The parasite infects most genera of humans and warm blooded animals. Toxoplasma gondii Dihydrofolate reductase (Tg DHFR) are attractive drug target for treating Toxoplasmosis. Molecular modeling techniques are now widely used in medicinal chemistry for design and optimization of inhibitors for a specific target. A pharmacophore model was generated using reported Tg DHFR inhibitors in PHASE module of Schrodinger suite, the pharmacophore model was able to accurately predict Tg DHFR activity. Further the molecules were subjected to molecular docking to understand the binding mode, the docking results also provide additional confidence in the proposed Pharmacophore model. Results suggested that the proposed 3D QSAR model and docking analysis can be useful to rationally design new inhibitors. A combined pharmacophore based and docking based virtual screening was performed to obtain a possible lead molecule for further optimization.