The effect of resistance training and a herbal supplement on muscular signaling pathways are limited. We investigated the expression of IL-6, Gp130, JAK and STAT after resistance training, and Spirulina platensis supplementation in animal muscle. Thirty-two male Sprague Dawley rats (weight: 290 ± 20 g, and 9 weeks of age) were divided into four groups: control (CO; n = 8), Spirulina platensis supplementation (SP; n = 8), resistance exercise (RE; n = 8), and Spirulina platensis + resistance exercise (SP + RE; n = 8). The resistance exercise group trained five sessions each week for eight weeks. Spirulina 200 mg kg −1 d −1 was used in the SP and SP + RE groups. Gene expression was measured by real-time PCR following the last training session. One-way ANOVA test with Tukey's post-hoc test were used for analysis of data (SPSS, version,21). Data analysis revealed that the expression of IL-6 (P = 0.001), Gp130 (P = 0.001), JAK (P = 0.0001) and STAT (P = 0.004) increased significantly in the RE group. The expression of IL-6 (P = 0.018), JAK (P = 0.001) and STAT (P = 0.001) in SP + RE group also increased significantly (P ≤ 0.05). SP showed a significant increase in Gp130 (P = 0.001) and STAT (P = 0.001). Supplementation by Spirulina platensis may enhance muscle accretion during resistance training.