Optical tweezers have become a popular manipulation and force measurement tool in cellular and molecular biology. However, there is still a lack of a sophisticated model for optical tweezers on trapping cells. In this paper, we present a novel model for optical tweezers to calculate the stiffness of trapping force upon a spherically symmetric Rayleigh sphere, which stimulates a common biological cell. A numerical simulation of this model shows that the stiffness of an optical tweezers system in trapping a cell is significantly smaller than that in trapping a polystyrene bead of the same size. Furthermore, under a small variant condition of the refractive index, the proposed model provides an approximate method which requires only the radial distribution of the trapped cell's refractive index for calculating the stiffness. (C) 2004 Elsevier B.V. All rights reserved.