Phosphatidylcholine (PC) is an essential compound for cell membranes, VLDL, cell signaling, and bile. PC can be synthesized directly from choline by the CDP-choline pathway or it can be synthesized via the methylation of phosphatidylethanolamine (PE) by phosphatidylethanolamine N-methyltransferase (PEMT). The latter of the two pathways requires methyl groups from three S-adenosylmethionines (SAM) and is responsible for [Difference]30% of the hepatic PC production. Other methyltransferases, including betaine-homocysteine S-methyltransferase (BHMT) and glycine N-methyltransferase (GNMT), have been shown to have increased activity with diabetes. Furthermore, GNMT has increased activity with all-trans-retinoic acid (ATRA) supplementation. This thesis explores the affects of diabetes and ATRA supplementation on phospholipid methylation by PEMT. I found a 2-fold increase in PEMT activity with diabetes alone and in combination with ATRA supplementation. ATRA administration alone had no affect on PEMT activity. PEMT activity has been proposed to be an important regulator of homocysteine levels. However, we found a 30-35% decrease in homocysteine levels in diabetes when PEMT activity was elevated. There were decreased plasma total homocysteine concentrations with ATRA administration, which had no affect on PEMT activity. There was also a significant decrease in PE and an increase in PC as a percentage of total phospholipids in the diabetic and ATRA supplemented groups. I hypothesized the increased PEMT activity was the result of increased betaine usage by BHMT in diabetes, leading to an effective choline deficiency. Upon supplementation with choline or betaine in the diabetic state, there was no change in PEMT activity. These data suggest PEMT activity may be altered by hormonal changes in the diabetic state, rather than by a lack of choline or betaine.