Objectives: This study aimed to evaluate physiological and microbiome differences in a murine model consuming a Mediterranean (M) v. Western (W) diet. Methods Study design: To investigate the potential of diets in modifying the fecal microbiota, we used 16 ICR mice per diet split evenly between males and females. Mice were acclimated for 5 weeks, consuming regular chow, before switching to M or W diets. Four same sex mice were housed per cage and randomly assigned M or W diets with 2 cages of male and female mice/diet. All animals were weighed weekly, and stool samples were collected, freeze-dried, and ground. An aliquot was analyzed for short-chain fatty acid (SCFA) to determine the fecal fermentation profile (FFP). Diets: All animals were acclimated to their surroundings while consuming the standard mouse chow diet for 5 wks. Experimental diets were from Envigo for 10 wks. M v.. W diets were 24.2v. 17.3% protein, 42.3 v. 48.5% carbohydrate, 13 v. 21.2 % fat, 9 v. 5% fiber, and energy density of 3.6 v. 4.5 kcal/g, and were offered ad libitum. Fecal Fermentation Profile: Fecal samples had SCFA extracted and analyzed using a modified Schwiertz et al. method via gas chromatography. The resulting SCFA profiles were used to determine differences between diets. Statistical Model: General linear models examined main effects of diet, sex, and week while accounting for baseline value and a random effect for cage (SCFA) or mouse (weight). Results: Diet effects for M v. W diets for SCFA were Acetate 50.12 v. 38.45% (p< 0.01), Propionate 14.19 v. 7.98% (p< 0.01), Butyrate 8.37 v. 17.27% (p< 0.01), Caproate 16.19 v. 23.68% (p< 0.01), and Caprillic 0.44 v. 0.68% (p< 0.01). Sex comparisons showed higher percentages of Butyrate (p< 0.05) for males and higher percentages of Isobutyrate (p< 0.01), Isovalerate (p< 0.01), and Propionate (p=0.02) for female mice. On the Mediterranean diet, male mice gained more weight than female mice, 4.96g v. 2.86g compared to baseline (p<0.01). Animals on a Western diet approached significance by gaining more weight (p<0.0871).