Aims: To put forward a scientific hypothesis about the progression of insulin-injection-induced lipohypertrophy (LH) according to the high-frequency ultrasonic imaging of insulin injection sites and the blood glucose control of patients. Methods: A total of 344 patients were screened for LH by means of high-frequency ultrasound scanning. The results of their ultrasound examination were described in detail and categorized into several subtypes. Seventeen patients with different subtypes of LH were followed up to predict the progression of LH. To further verify our hypothesis, the effects of different types of LH on glycemic control of patients were observed by comparing glycated hemoglobin A1c (HbA1C) and other glycemic-related indicators. Results: LH was found in 255 (74.1%) patients. According to the high-frequency ultrasonic imaging characteristics, LH can be categorized into three subtypes in general. Among all the LHs, the most common type observed was nodular hyperechoic LH (n= 167, 65.5%), followed by diffuse hyperechoic LH (n= 70, 27.5%), then hypoechoic LH (n= 18, 7.0%). At the follow-up after six months, all 10 patients with nodular hyperechoic LH had LH faded away. Of the five patients with diffuse hyperechoic LH, two had inapparent LH, and three had diffuse hyperechoic parts which had shrunk under ultrasound. No obvious changes were observed in the two cases of hypoechoic LH. Compared with the LH-free group, the mean HbA1Cof the nodular hyperechoic LH group increased by 0.8% (9 mmol/mol) (95% CI:−1.394~−0.168,p= 0.005), that of the diffuse hyperechoic LH group increased by 2.0% (21 mmol/mol) (95% CI: −2.696~−1.20,p< 0.001), and that of the hypoechoic LH group increased by 1.5% (16 mmol/mol) (95% CI: −2.689~−0.275,p= 0.007). Conclusions: It was hypothesized that the earlier stage of LH is nodular hyperechoic LH. If nodular LH is not found in time and the patient continues to inject insulin at the LH site and/or reuse needles, LH will develop into a diffuse type or, even worse, a hypoechoic one. Different subtypes of LH may represent differences in severity when blood glucose control is considered as an important resolution indicator. Further studies are needed to confirm our hypothesis on the progression and reversion of insulin-induced lipohypertrophy.