Wayne Arendse, Jose Meza and Jeremy Brockie all started as the Brazilians searched for their second successive win in the league having defeated Polokwane City two weeks ago.
Mosimane's counter-part, Owen Da Gama, made four changes to the side that started in the 2-2 against Black Leopards.
Lindokuhle Mbatha, who was once on the books of Sundowns, faced his former side as the Lions of the North looked to secure their first win of the season.
The hosts combined nicely in the opening stages of the game with Themba Zwane and Gaston Sirino causing havoc for the visitors backline which was without Bevan Fransman.
The experienced defender, who joined the reigning National First Division (NFD) champions from Maritzburg United last month, was surprisingly left on the bench by Da Gama.
Highlands Park were hoping to avoid another drubbing at the hands of Sundowns having succumbed to a 5-0 defeat to the Tshwane giants at the same venue in a PSL match during the 2016/17 season.
They looked solid and organized at the back with the Brazilians struggling to supply their main striker Brockie upfront.
The New Zealand marksman was hoping to grab his first competitive goal for the Brazilians. He went into this match having failed to score in 10 league games since joining Downs from SuperSport United last January.
Highlands defender Sello Motsepe produced a great defensive block to deny Brockie, who was looking to net from close range with Meza having delivered a good cross which proved to be the last chance of the first half.
The score was 0-0 at the interval with a resilient Highlands Park side containing a much-fancied Sundowns team.
Sundowns suffered were dealt a major blow a few minutes into the second half as they were reduced to 10 men following Ricardo Nascimento's red card.
Mosimane reacted by sacrificing Brockie, who was a busy man for the hosts in the first half, and the former Bafana Bafana coach introduced Motjeka Madisha as he changed his tactical approach.
The Lions of the North, who went into the encounter having scored 33.3% of their goals in the final 15 minutes of the game in the league, pressed Sundowns as they looked to use their numerical advantage to effect.
However, the defending PSL champions looked dangerous on the counter, and they were unfortunate not to break the deadlock in the closing stages of the game with Highlands' defence exposed.
Sirino played a delightful cross into the opposition box, finding Wayne Arendse who beat Tapuwa Kapini with a good header only for his effort to cleared off the line by Junior Sibande.
Sundowns and Highlands launched attack after attack in the closing stages of the game in search of a late winner, but it did not come and ultimately, the game ended in a 2-2 draw.
With this draw, the Brazilians are now placed fifth on the league standings, while the Lions of the North climbed up to 11th on the log.