In a method of manufacturing a CMOS image sensor, a P type epitaxial layer is formed on an N type substrate. A deep P+ type well layer is formed in the P type epitaxial layer. An N type deep guardring well is formed in a photodiode guardring region. The N type deep guardring region makes contact with the N type substrate and also be connected with an operational voltage terminal. A triple well is formed in a photodiode region and a peripheral circuit region. The triple well is used for forming a PMOS and an NMOS having different operational voltages. An isolation region is formed in the photodiode region. The isolation region in the photodiode region has a depth different from a depth of an isolation region in the peripheral circuit region.