Objective To compare the pathological characteristics and transcriptome differences among three rat models of myocardial hypertrophy (CH) induced by transverse aortic constriction (TAC), isoproterenol (ISO), and spontaneous hypertension (SHR). Methods Male SD and SHR rats (control group: WKY) were used to establish three models. For the TAC experiment, SD rats were divided into a sham group (n= 5) and TAC group (n= 14). Rats in the TAC group underwent TAC surgery and the sham group underwent a sham operation. Each group of rats were fed for 5 weeks after the operation. For the ISO experiment, SD rats were randomly divided into a control group (C) (n= 5) and ISO group (n= 11). Rats in the ISO group received multiple subcutaneous injections of 5 mg/ (kg·d) ISO on the back of the neck, whereas the control group was injected with the same dose of saline twice daily for 10 days. For the spontaneous hypertension?mediated CH experiment, SHR rats were considered as the model group (n= 5) and WKY rats as the control group (n= 5). All rats were normally fed to 16 weeks of age. Echocardiography was performed and plasma ANP levels were measured to determine whether the CH rat model was established successfully. Then, survival rates, blood pressure, hemodynamics, and the cardiac mass index were calculated. Heart tissues were stained with HE, Masson, and wheat germ agglutinin (WGA). Transcriptome sequencing was performed in myocardial tissue to screen differentially expressed genes and analyze their pathways. The sequencing result were verified by quantitative real?time PCR ( qRT?PCR). Results Plasma ANP in each model group was significantly higher than that in the control group (P< 0.05). IVSd, IVSs, LVPWd, and LVPWs in TAC and ISO model rats and LVSd in SHR rats were significantly increased (P< 0.05), while LVIDd and LVIDs were significantly decreased (P< 0.05) compared with those in the control group. The survival rates of model rats in each group were 100% for SHR, 81.82% for ISO, and 35.71% for TAC. Compared with control groups, the blood pressure of model rats in TAC and ISO groups was significantly decreased (P< 0.05), whereas that of the SHR group was significantly increased (P< 0.01). HW/ BW and LVW/ BW ratios in each model group were increased significantly (P< 0.05). Hemodynamics showed that HR, LVESP, LVEDP, and dP/ dtmax were significantly decreased in model rats of TAC and ISO groups (P< 0.01), whereas all indexes in SHR rats were significantly increased (P<0.01). The myocardial tissue of TAC and SHR model rats showed a heterogeneous network of reactive interstitial fibrosis, whereas ISO rat myocardial tissues had a large area of repaired interstitial fibrosis. The cross?sectional area of the myocardium in TAC and ISO groups was increased significantly (P< 0.05), but there was no significant difference in SHR rat. In total, 175, 568, and 279 differentially expressed genes were identified by transcriptome sequencing in TAC, ISO, and SHR models, respectively. Autophagosome, cancer?related signaling pathway, and PI3K/ AKT pathway were co?enriched in the three model groups, while drug response, relaxin signaling, and JAK/ STAT signaling pathways were only enriched in TAC, ISO, and SHR model groups. qRT?PCR result were consistent with the transcriptome sequencing data. Conclusions CH was successfully established in TAC? and ISO?treated rats and spontaneously hypertensive rats. The survival rate, blood pressure, hemodynamics, degree of myocardial hypertrophy, histopathological characteristics, and gene expression profiles in CH model rats were influenced by various induced factors.