<p>To elucidate the contributions of M-cone to the negative off-response of rat Electroretinogram (ERG) using specific drugs and spontaneous mutation rat models. The ON/OFF responses of ERG were evoked by long duration flash (200 ms) pre or post the application of 2-amino-4-phosphonobutyric acid (APB), cis-piperidine-2,3-dicarboxylic acid (PDA) or BaCl₂ to the Sprague-Dawley (SD) rats. Furthermore, the ON/OFF responses of other two types of mutation rats, the middle-wavelength opsin cone dysfunction (MCD) rats and congenital stationary night blindness (CSNB) rats, were recorded. Typical scotopic and photopic ON/OFF responses were recorded in SD rats. At light offset, the OFF response showed a rapid negative deflection, then the retinal potential slowly returned to baseline from the trough of the negative off-response. The negative off-response was completely eliminated by the intravitreal injection of 400 µM APB. The amplitude of the negative off-response was reduced by the application of 5 mM PDA. However, the off component was not blocked by the application of 50 µM BaCl₂. In addition, distinct differences of OFF response were found among MCD, CSNB and SD rats. The scotopic ON/OFF ERG of the MCD and CSNB rats showed no obvious negative off component at light offset, while the negative off component of photopic ON/OFF ERG was found in the CSNB rats, though with lower amplitude. The negative off-response of rat ERGs is not the off component of M-wave: a negative potential change at stimulus onset or offset. M-cone and the depolarizing bipolar cell play a central role in the signal transmission of this negative off-response.</p>