Microcirculation is defined as the blood flow in the smallest blood vessels. Laser speckle contrast imaging (LSCI) is a full field imaging technique that provides instantaneous 2-D perfusion maps of illuminated tissues based on speckle contrast. Perimed’s Perfusion Speckle Imager (PSI) is a medical device developed at Perimed AB that exploits LSCI to measure tissue blood perfusion. In this thesis work, a robust Autofocus (AF) algorithm for PSI was implemented. AF is a procedure to drive PSI camera to reach the depth of focus and acquire sharp images, that relies only on signal processing. Therefore, several Blind image sharpness assessment (BISA) methods, to judge the degree of image sharpness, were compared to choose which BISA method to incorporate in the algorithm. An optimized focus scanning technique was implemented to more efficiently find the depth of focus. When working with LSCI, speckle is a source of noise that destroys image content. Experiments were performed to study laser speckle filtration: digital filters were employed to attenuate the speckle noise that corrupted details in the acquired images. Finally, two methods to perform AF were provided. These procedures were proven practically with LED images. However, with laser source image information is corrupted by speckle despite the application of digital filters and AF remains a real challenge. Moreover, important hardware limitations require to be overcome to make the technique real-time. Focus motor speed should be higher to acquire images at different focus positions faster which could benefit the speed of the AF procedure and speckle filtration.