One of the most important machining processes in the field of orthopedic surgeries and biomedical engineering is the drilling process. Applying excessive forces on the bone tissue, it can be caused cracking and damage bone tissue during the drilling process. In this paper, it is produced an improved analytical model based on early work done by Bono and Ni, Chandrasekharan, and Lee to predict the thrust force in the bone drilling process. In this model, the cutting action at the drill point is divided into three regions: the primary cutting lips, outer portion of the chisel edge (the secondary cutting edges), and inner portion of the chisel edge (the indentation zone). All three regions have been investigated for the cutting process by the analytical model. In order validating the model, some experiments performed on the fresh bovine bone. Feed rate and rotational speed are adapted as the effective parameter in the drilling process, The statistical model to obtain the mathematical model and provide interaction diagrams of input variables experiments, to response surface methodology and experimental investigation of bone drilling have been offered. Comparing the analytical model and experimental results show good agreement. From both analytical model and experiments, it is can conclude that with decreasing feed rate and increasing rotational speed, thrust force on the bone tissue decreases.