Systems thinking is the ability to reason about biological systems in terms of their characteristics and can assist students in developing a coherent understanding of biology. Literature reports about several recommendations regarding teaching systems thinking, while it seems that systems thinking has not reached classroom practice. The main aim of this study was to identify design guidelines to implement systems thinking in upper-secondary biology education. Based on the recommendations of literature and experience a teacher team developed, tested and evaluated two lessons in two upper-secondary biology classes (15-16 years old students, n = 26, n = 19) using Lesson Study. Lesson one focused on the application of seven system characteristics: boundary, components, interactions, input & output, feedback, dynamics, and hierarchy. Lesson two focused on the improvement of students' understanding of the characteristics feedback and dynamics by using a qualitative modelling approach. Based on classroom observations, student products and interviews, the results suggest that a first step is made: most students are able to name and apply the seven characteristics. It seems important to pay attention to the: (1) introduction of the seven characteristics; (2) application of the characteristics in a wide variety of contexts; (3) individual characteristics; (4) explicit use of system language.