Superoxide dismutases (SODs) convert the superoxide radical to hydrogen peroxide and molecular oxygen and play crucial roles in plant tolerance to oxidative stress. Expression of many genes encoding SODs are promoted in response to environmental stresses, but the exact mechanism of such promotion is largely unknown. Here, we report that MKK5, a mitogen-activated protein kinase kinase, mediated the high light-induced expression of genes of two copper/zinc SODs, CSD1 and CSD2, and was involved in the oxidative adaptation to high light stress. In response to high light, wild-type Arabidopsis plants showed much enhanced expression of CSD1 and CSD2 and higher enzyme activity of MKK5. In the MKK5-RNAi lines, however, the induction of CSD1 and CSD2 as well as the activation of MKK5 activity were completely arrested. In contrast, over-expression of MKK5 promoted the expression of CSD1 and CSD2. MKK5-RNAi gene silencing and CSD1/2-RNAi suppression plants became much more sensitive to high light stress than wild-type plants, and the double mutant of mkk5 csd1 exhibited hypersensitivity to the stress. Plants over-expressing MKK5 showed enhanced tolerance to high light stress. Our results demonstrate that MKK5 mediated a signal of the high light-induced expression of genes CSD1 and CSD2. Manipulating the MKK5 and thereby up-regulating the levels of CSD1 and CSD2 transcripts can improve plant tolerance to high light stress.