According to Wolf and Richard′ s vectorial diffraction integral, a model is established, and the point spread function (PSF) in the two common conditions of confocal microscopy with a refractive index mismatch to study the effect of aberration induced by refractive index mismatch on imaging in confocal microscopy. The model is tested by experiment. When the beams focus into a spot through oil, coverslip and water, the full width at half maximum (FWHM) of the PSF along the z axis is broadened from 0.4391 μm to 0.931 μm with the detective depth from 0.5 μm to 10 μm . And the maximum intensity of the PSF is reduced from 1.161 to 0.4119. When the detective depth is 10 μm , the FWHM of the PSF with the refractive index match along the z axis is 1.059 μm , and its maximum intensity is 1. But the FWHM of the PSF with refractive index mismatch along the z axis is 7.5 μm , and its maximum intensity is 0.04632. When the detective depth is large, the aberration induced by refractive index mismatch can make light spot bigger, dispersive energy and influent the imaging quality.