PURPOSE: Leukemia inhibitory factor (LIF) and Follistatin like-1 (FSTL1) are myokines involved in the inflammatory response, and have been suggested to be involved in muscle adaptation. The purpose of this study was to characterize the LIF and FSTL1 response to a high intensity (HI) and high volume (HV) bout of resistance exercise (RE) before (PRE) and after (POST) 7 weeks of HI and HV resistance training (RT). METHODS: Twenty resistance trained men (23.5±2.6 y, 1.79±0.05 m, 75.7±13.75) volunteered for this study. Following a 2-week preparatory phase, participants were randomized into either a HV (n = 10, 4 x 10-12RM, 1-min rest) or HI (n = 10, 4 x 3-5RM, 3-min rest) training protocol for 7 weeks (4 d·week-1). Blood draws were obtained prior to (BL), immediately (IP), 30 min (30P), and 60 min (60P) post-exercise at PRE and POST. Plasma LIF and FSTL1 concentrations were determined using a multiplex signaling assay kit and analyzed with MAGPIX® technology. Area under the curve (AUC) for each myokine was calculated via the trapezoidal method. Data were analyzed using a repeated measures ANOVA. When appropriate, post-hoc analysis using unpaired t-tests were conducted with Bonferroni corrections. In addition, bivariate relationships were examined using Pearson product-moment correlations. RESULTS: A significant (p=0.021) training x time interaction was observed for LIF. No main effect of time (p=0.262) was observed at PRE, but was at POST (p=0.025). LIF concentrations at 60P (13.29 pg[BULLET OPERATOR]mL-1) trended (p=0.083) towards an attenuation from BL concentrations (32.67 pg[BULLET OPERATOR]mL-1). A significant main effect of time was also observed for FSTL1. FSTL1 concentrations at 60P (6693 pg[BULLET OPERATOR]mL-1) were significantly (p=0.013) lower compared to IP (7542 pg[BULLET OPERATOR]mL-1) when collapsed across PRE and POST. Significant correlations were noted between ΔBLLIF and ΔBLFSTL1(r=0.834, p=0.01), and between ΔAUCLIF and ΔAUCFSTL1 (r=0.809, p=0.01). CONCLUSIONS: LIF concentrations were attenuated at 60P in response to an acute bout of RE after 7-weeks of training. Similarly, FSTL1 concentrations, collapsed across groups, were attenuated after exercise. Changes in LIF were highly correlated to changes in FSTL1 suggesting that adaptations regulating these myokines may be linked.