Although it has been shown that telomerase has neuroprotective effects, mainly as a result of its non-canonical functions in neuronal cells, its role with respect to glial cells remains unknown. There is growing evidence indicating that telomerase plays an important role with respect to inflammation, especially in the regulation of pro-inflammatory cytokine gene expression. The present study aimed to evaluate the role of telomerase in an astrocyte cell model treated with palmitic acid (PA) and tibolone. Cell death, reactive oxygen species production and interleukin-6 expression were evaluated under telomerase inhibition with the BIBR1532 compound in T98G cells treated with tibolone and PA, using fluorometry, flow cytometry, enzyme-linked immunosorbent assays and the quantitative polymerase chain reaction. The results obtained showed that telomerase protein was increased by PA after 36 hours, alone or in combination with tibolone, and that its activity was affected by PA. Telomerase inhibition reduced interleukin-6 expression and it interfered with the protective effects of tibolone on cell death. Moreover, tibolone increased Tyr707 phosphorylation in PA-treated cells. In the present study, we provide novel findings about the regulation of telomerase by PA and tibolone. Telomerase was involved in inflammation by PA and in protective effects of tibolone. Therefore, we conclude that telomerase could play a dual role in these cells.