High homocysteine (Hcy) levels are a well-known independent risk factor for endothelial damage in atherosclerosis. We examined whether a rat intestinal model of ischemia-reperfusion was associated with high Hcy and with the modification of plasma albumin into cysteinylated species (CysAlb). The three treatment groups were as follows: midline abdominal incision (group A, n=10), followed by ligation of the superior mesenteric artery for a period of 2h (group B, n=3), and followed by reperfusion for 1h (group C, n=10). Hcy levels were 2.5-fold higher in group C than group A (p<0.05). 100% and 73.44+/-0.04% of Alb were modified into Cys species in groups C and B, respectively, compared to 51.2% in group A. A cystathionine beta-synthase (CBS) deficient mouse model, known to have high plasma Hcy levels, was also used to determine the extent of CysAlb. Hcy levels, %CysAlb, and %HcyAlb were 180.1+/-45.7 microM, 0%, and 23.4+/-4.4% in CBS deficient mice, while in control mice, those values were 5.7+/-1.8 microM, 24.2+/-4.1%, and 0%, respectively (p<0.05). High CysAlb and Hcy levels were observed in a rat model of bowel ischemia/reperfusion while high HcyAlb and Hcy levels with no CysAlb were observed in the CBS deficient mice. CysAlb may serve as a biomarker for the severity of gut ischemia, and high Hcy may explain endothelial damage associated with this model. Additionally, active CBS is essential for the formation of CysAlb.