The present study utilized an acute bout of resistance exercise to examine the effects on the immune- and inflammatory-related genes in peripheral blood mononuclear cells (PBMCs). To date, only a limited number of gene transcripts related to the immune and inflammatory processes have been examined. Ten resistance-trained men (20-24 yrs), with at least 2 yrs resistance exercise training (RET) experience performed an acute bout of RET for ∼30 min following a 12 hr fast. The RET included the back parallel squat and leg press at 45% & 55% of 1-RM for 2 sets and 65% of 1-RM for the following 4 sets. All exercises were performed with a 2:2 cadence followed by 2 min rest periods. Venous blood was sampled at rest, immediately following exercise, and at 2 hr post-exercise and analyzed for total and differential leukocytes and global gene expression using Affymetrix Genechips. Results showed that leukocytes, monocytes, lymphocytes, and lactate values were elevated immediately post-exercise (p<0.05) over baseline. At 2 hr post-exercise, leukocytes and granulocytes remained elevated (p<0.05), whereas lymphocytes were lower than (p<0.05) baseline values. RET induced transient fluctuations in immune cells. Initial microarray results indicate that gene expression signatures are highly correlated with peripheral blood mononuclear counts and that differentially expressed genes supported the immunophenotyping results. At the 2 hr recovery time point, matrix metalloproteinase 9 (MMP 9), orosomucoid 1 (ORM 1) and arginase 1 (ARG 1) all showed significant up regulation, while the gene CD160 was down regulated. These results demonstrate that an acute bout of RET disrupts cellular homeostasis, induces a transient redistribution of certain leukocytes, and results in a transcriptional change in blood samples consistent with phenotyping results that differs from aerobic exercise.