Inflammatory disease is initiated by leukocytes (white blood cells) rolling along the inner surface lining of small blood vessels called postcapillary venules. Studying the number and velocity of rolling leukocytes is essential to understanding and successfully treating inflammatory diseases. Potential inhibitors of leukocyte recruitment can be screened by leukocyte rolling assays and successful inhibitors validated by intravital microscopy. In this paper, we present an active contour or snake-based technique to automatically track the movement of the leukocytes. The novelty of the proposed method lies in the energy functional that constrains the shape and size of the active contour. This paper introduces a significant enhancement over existing gradient-based snakes in the form of a modified gradient vector flow. Using the gradient vector flow, we can track leukocytes rolling at high speeds that are not amenable to tracking with the existing edge-based techniques. We also propose a new energy-based implicit sampling method of the points on the active contour that replaces the computationally expensive explicit method. To enhance the performance of this shape and size constrained snake model, we have coupled it with Kalman filter so that during coasting (when the leukocytes are completely occluded or obscured), the tracker may infer the location of the center of the leukocyte. Finally, we have compared the performance of the proposed snake tracker with that of the correlation and centroid-based trackers. The proposed snake tracker results in superior performance measures, such as reduced error in locating the leukocyte under tracking and improvements in the percentage of frames successfully tracked. For screening and drug validation, the tracker shows promise as an automated data collection tool.