Salient features of the current study are as follows: (i) in the retina, diabetes upregulates MMP-9 and downregulates TIMP-1 expression in a time-dependent manner; (ii) U0126, a specific inhibitor of ERK1/2, attenuates early diabetes-induced upregulation of MMP-9 and enhanced TIMP-1 expression; (iii) U0126 attenuates diabetes-induced upregulation of iNOS, IL6, and TNF-α in the retina; (iv) knockdown of MMP-9 prevents diabetes-induced upregulation of iNOS level in the retina. Here, TIMP1 is linked to diabetes mellitus.