The changes of intrinsic optical signals (IOS) are one of the important parameters of spreading depression (SD). The relationship between cerebral blood flow (CBF) and IOS can provide useful information for understanding the role of SD in neurological disorders. Here, we combined laser speckle imaging (LSI), intrinsic optical signal imaging (IOSI), and electrophysiological recording techniques to study the effect of CBF before the occurrence of SD on the spatiotemporal characteristics of IOS related to SD in a ministroke model. Four kinds of temporal pattern of changes in IOS were observed at cortical locations with different level of the CBF before the occurrence of SD. The results indicate that in the surrounding of micro-infarcts, SD-associated IOS vary as a function of blood flow rate, suggesting that the characteristics of IOS during SD might reflect blood flow rates.