We have developed and demonstrated the use of a dedicated CMOS device for in vivo functional imaging of the mouse brain. In order to achieve this, a 176 x 144 pixel array image sensor is designed, fabricated and specially packaged using a novel process. By using on-chip fluorescence imaging configuration, we have successfully imaged deep inside the hippocampus of the mouse brain. Functional imaging is verified by using a fluorogenic substrate that detects the presence of serine protease in the brain. Introduction of kainic acid induces the expression of the serine protease. The protease reacts with the substrate which then fluorescence. By imaging and measuring the fluorescence signal, we have successfully measured the brain protease activity and accurately determined its reaction onset. This method represents a novel approach for neural imaging.