The glycation of plasma proteins leading to the production of advanced glycation end products (AGEs) and subsequent damage is a driving factor in the pathophysiology of diabetic complications. The overall research objective was to elucidate the mechanisms by which birds prevent protein glycation in the presence of naturally high plasma glucose concentrations. This was accomplished through the specific purpose of examining the impact of temperature and glucose concentration on the percent glycation of chicken serum albumin (CSA) in comparison to human serum albumin (HSA). Purified CSA and HSA solutions prepared at four different glucose concentrations (0 mM, 5.56 mM, 11.11 mM, and 22.22 mM) were incubated at three different temperatures (37.0°C, 39.8°C, and 41.4°C) on separate occasions for seven days with aliquots extracted on days 0, 3, and 7. Samples were analyzed by LC-ESI-MS for percent glycation of albumin. The statistically significant interaction between glucose concentration, temperature, albumin type, and time as determined by four-way repeated measures ANOVA (p = 0.032) indicated that all independent variables interacted to affect the mean percent glycation of albumin. As glucose concentration increased, the percent glycation of both HSA and CSA increased over time at all temperatures. In addition, HSA was glycated to a greater extent than CSA at the two higher glucose concentrations examined for all temperature conditions. Temperature differentially affected percent glycation of HSA and CSA wherein glycation increased with rising temperatures for HSA but not CSA. The results of this study suggest an inherent difference between the human and chicken albumin that contributes to the observed differences in glycation. Further research is needed to characterize this inherent difference in an effort to elucidate the mechanism by which birds protect plasma proteins from glycation. Future related work has the potential to lead to the development of novel therapies to prevent or reverse protein glycation prior to the formation of AGEs in humans, thus preventing the development and devastating effects of numerous diabetic complications.