Laser therapy (LRx) may affect the retinal ganglion cells (RGC), which play a role in circadian rhythms. This study assesses the effect of LRx on the circadian variation of cortisol (F), measured in 20 Type 2 diabetic patients (DM), 10 following LRx for diabetic proliferative retinopathy (DPR), and 10 control (CTR) without laser Rx or retinopathy. The diurnal F variation in the CTR followed a normal pattern. Compared with CTR, the F levels of the DPR group were significantly higher at 1600 and 2400 h (10.2+/-2.5 vs. 6.9+/-4.0 microg/dl, P<.05, and 6.4+/-2.5 vs. 2.6+/-1.7 microg/dl, P<.001, respectively). These results provide evidence that DM patients, following bilateral LRx for proliferative diabetic retinopathy, experienced nocturnal hypercortisolemia and loss of normal circadian cortisol variation, probably secondary to LRx damage to the RGC.