The expression and influence mechanism of CTGF and HO-1 in rats with diabetic retinopathy (DR) was investigated. One hundred and thirty male Sprague-Dawley (SD) rats were selected and randomly divided into the control group and DR group, with 65 rats in each group. DR was caused by intraperitoneal injection of streptozotocin in rats in the DR group. There were 55 successful models and 10 failed in the modelling. The successful models were sacrificed at the 2nd, 4th and 6th month, respectively. RT-qPCR technology was used for detection of the expression of CTGF and HO-1 in rat retina in each group, H&E staining for observation of the gradation structure in rat retina and TUNEL method for detection of apoptosis of retinal cells. In the DR group, the retina layers were disordered and a few blood vessels dilated at the 2nd month. In the DR group, the inner membrane of the retina swelled, and the ganglion cells were irregularly arranged at the 4th month. In the DR group, dilatation of the blood vessels was more obvious, the inner membrane edema was more severe, and the arrangement was more irregular at the 6th month. The retinal apoptosis rate of DR rats gradually increased at the 2nd, 4th and 6th month, after which, the CTGF expression gradually increased, but the HO-1 expression gradually decreased in retina in the DR group. However, the mRNA expression of CTGF and HO-1 in the rats at the 2nd, 4th and 6th month in the DR group was higher than that in the control group at the same period. Therefore, CTGF and HO-1 are associated with the occurrence and development of DR in rats and can be considered as targets for the treatment of DR.