Protein kinase C theta (PKC-${ heta}$) is a serine/threonine specific protein kinase. It is largely expressed in the T-cells and CD28 signaling. PKC-${ heta}$ phosphorylates diverse proteins that are involved in the various cellular signaling pathways. Activated PKC-${ heta}$ in turn activates other transcription factors that control the proliferation and differentiation of T- cells. PKC-${ heta}$ is considered to be an interesting therapeutic target due to its crucial role in the proliferation, differentiation and survival of T-cells. In the present study, we have performed ligand-based CoMFA study on a series of pyridylpyrazolopyridine derivatives as PKC-${ heta}$ inhibitors. An acceptable CoMFA model ($q^2$=0.544; ONC=4; $r^2$=0.876) was developed and validated by Bootsrapping and progressive sampling. The CoMFA contour map suggested the regions to increase the activity. Bulky substitutions in R2 position of the piperizine ring could increase the activity. Similarly positive, small substitution in the R1 position of the Pyridine ring could considerably increase the activity. Our work could assist in designing more potent PKC-${ heta}$ inhibitors of pyridylpyrazolopyridine derivatives.