The present invention relates to a system and method for reducing image artifacts for a CMOS camera used as an optical detector for a line confocal fluorescent imager. The method for reducing image artifacts in a monochromatic image comprises subtracting RGB channel offset mismatch; and correcting random row offset for each row. Preferably, the method also comprises correcting random column offset and gain. Optionally, the method also comprises clipping of defective pixels, and/or subtracting dark current. When the monochromatic image is a fluorescence image, the method also comprises a step of compressing CMOS camera noise. Also provided are a system for reducing image artifacts in a monochromatic image from a CMOS camera, as well as an image artifact reduction system for a CMOS camera-based line confocal fluorescent microscope.