Depression and cardiovascular disease are known to occur simultaneously, but the reason for this is unclear. Although total peripheral resistance is often increased in both conditions no detailed description is available. We aimed to study changes in resistance artery function during development of stress induced depression. We have studied the middle cerebral (CA), femoral (FA) artery, and mesenteric small arteries (MSA). Rats under chronic mild stress (CMS) were used. In this model, only some rats develop anhedonia- like condition (proved by sweat water intake), while others do not show signs for anhedonia (stress-resilient). We have assessed isometric force development in isolated arteries in vitro after 4 and 8 weeks exposure to variable and unpredictable stressors (e.g. sound, air blow, light flicker etc). At 4 weeks MSA from CMS rats developed higher maximal tension to noradrenalin (NA) than non- stressed controls. Moreover, MSA from anhedonic rats were more sensitive to NA than the resilient group. This difference disappeared in the presence of cocaine consistent with reduced neuronal reuptake of NA in anhedonic rats. In contrast, at 8 weeks MSA from all three groups responded similar to NA, but cocaine unmasked elevated NA sensitivity of MSA from anhedonic rats. At 4 weeks CA from the CMS groups were slightly less sensitive to serotonin (5-HT), but at 8 weeks CA from depressed rats were more sensitive to 5-HT in comparison to the resilient and non-stressed groups. FA from anhedonic rats demonstrated increased maximal tension to NA at 4 and 8 wks in comparison to the control and resilient groups. The observed changes correlated with changes in corticosterone, which transiently increased to stress. Thus, our results indicate that depression is associated with changes in the contractility and agonist sensitivity of resistance arteries. These changes assume to be important for the cardiovascular events associated with depression.