The present study aimed to reveal the underlying mechanism of angiotensin II (AngII)‑induced cardiac remodeling and to identify potential therapeutic targets for prevention. Rat cardiac fibroblasts (CFs) were cultured with 10 nM AngII for 12 h, and CFs without AngII were used as the control. Following RNA isolation from AngII treated and control CFs, RNA‑sequencing was performed to detect gene expression levels. Differentially‑expressed genes (DEGs) were identified using the linear models for microarray analysis package in R software, and their functions and pathways were examined via enrichment analysis. In addition, potential associations at the protein level were revealed via the construction of a protein‑protein interaction (PPI) network. The expression levels of genes of interest were validated via reverse transcription‑quantitative polymerase chain reaction analysis. In total, 126 upregulated and 140 downregulated DEGs were identified. According to the enrichment analysis, acetyl coA carboxylase β (ACACB), interleukin 1β (IL1B), interleukin 1α (IL1A), nitric oxide synthase 2 (NOS2) and matrix metallopeptidase 3 (MMP3) were associated with the immune response, regulation of angiogenesis, superoxide metabolic process and carboxylic acid binding biological processes. Among them, ACACB and MPP3 were two predominant nodes in the PPI network. In addition, IL1B and MMP3 were demonstrated to be upregulated. These five genes, particularly IL1B and MMP3, may be used as candidate markers for the prevention of AngII‑induced cardiac remodeling.