Accumulating evidence has highlighted the potential of microRNAs (miRs) as biomarkers in various human diseases. However, the roles of miRs in bacterial meningitis (BM), a severe infectious condition, still remain unclear. Thus, the present study aimed to investigate the effects of miR-135a on proliferation and apoptosis of astrocytes in BM. Neonatal rats were injected with Streptococcus pneumoniae to establish the BM model. The expression of miR-135a and hypoxia-inducible factor 1α (HIF-1α) in the BM rat models were characterized, followed by determination of their interaction. Using gain- and loss-of-function approaches, the effects of miR-135a on proliferation, apoptosis, and expression of glial fibrillary acidic protein (GFAP), in addition to apoptosis-related factors in astrocytes were examined accordingly. The regulatory effect of HIF-1α was also determined along with the overexpression or knockdown of HIF-1α. The results obtained indicated that miR-135a was poorly expressed, whereas HIF-1α was highly expressed in the BM rat models. In addition, restored expression levels of miR-135a were determined to promote proliferation while inhibiting the apoptosis of astrocytes, along with downregulated Bax and Bad, as well as upregulated Bcl-2, Bcl-XL, and GFAP. As a target gene of miR-135a, HIF-1α expression was determined to be diminished by miR-135a. The upregulation of HIF-1α reversed the miR-135a-induced proliferation of astrocytes. Taken together, the key findings of the current study present evidence suggesting that miR-135a can downregulate HIF-1α and play a contributory role in the development of astrocytes derived from BM, providing a novel theoretical perspective for BM treatment approaches.